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Sleeve-related thrombosis: a new form of catheter-related thrombosis.

In a detailed study of central venous catheter-related sleeve and thrombosis in experimental animals, a new form of thrombosis was detected and termed sleeve-related thrombosis. A silastic catheter was placed in the jugular vein and the anterior vena cava of 22 rabbits and 54 rats. After intervals of 1, 3, 7 days, 2, 3, 4 weeks and 1, 2, 4, 6 months the veins were examined by light microscopy and by transmission electron microscopy. In about 50% of the rats a thrombus was observed at the end of the catheter sleeve. Consecutive cutting allowed the visualization of a transition from a sleeve via part of sleeve and part of thrombus to a pure thrombus. This thrombus was separated from the vein wall and could not be considered a mural thrombus. As the thrombus was only attached to the terminal part of the organized catheter sleeve we propose the name sleeve-related thrombosis.

Animals↗

Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis. Pinede L, Ninet J, Duhaut P et al for the Investigators of the 'Durée Optimale du Traitement Antivitamines K' (DOTAVK) study. Circulation 2001; 103: 2453-60.

QUESTION: Is anticoagulant treatment for calf vein thrombosis for 6 weeks duration associated with acceptable recurrence and safety outcomes? Is anticoagulant therapy for 3 months duration for proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) associated with acceptable recurrence and safety outcomes? POPULATION: Men and women with a first episode of symptomatic calf vein thrombosis or proximal DVT confirmed by ultrasound or venography, or PE confirmed by lung scan or angiography. Patients with pregnancy, thrombophilia, severe PE, and cancer were excluded. DESIGN AND METHODS: After treatment with heparin and oral anticoagulants targeting an INR of 2-3, patients with calf DVT were randomized to 6 weeks (n = 105) versus 3 months (n = 92) of treatment, and patients with proximal DVT and/or PE were randomized to 3 months (n = 270) versus 6 months (n = 269) of treatment. The outcome events were recurrences and major, minor, or fatal bleeding complications. The mean follow-up time was 12 months. RESULTS: A total of 736 patients were enrolled. For calf vein thrombosis the recurrence of DVT or PE after 6 weeks of therapy was 2/105 (2.0%) versus 3/92 (3.4%) with 3 months of therapy, relative risk of 0.58 (95% CI: 0.10-3.36). The rates of major bleeding were 1/105 (1.0%) and 3/92 (3.4%) respectively, relative risk of 0.29 (95% CI: 0.03-2.72). For proximal DVT or PE, the recurrence rate after 3 months of therapy was 21/270 (8.1%) versus 23/269 (8.7%) after 6 months of treatment, relative risk of 0.93 (95% CI: 0.53-1.65). The rates of major bleeding were 5/270 (1.9%) versus 7/269 (2.6%) respectively, relative risk of 0.73 (95% CI: 0.24-2.27). CONCLUSION: After isolated calf vein DVT, 6 weeks of oral anticoagulation is sufficient. For proximal DVT or PE, 3 and 6 months of anticoagulant therapy is equivalent. For patients with temporary risk factors who have a low risk of recurrence, 3 months of treatment seems to be sufficient.

Administration, Oral↗

An instrument for measuring health-related quality of life in patients with Deep Venous Thrombosis (DVT): development and validation of Deep Venous Thrombosis Quality of Life (DVTQOL) questionnaire.

BACKGROUND: Few studies have evaluated patient-reported outcomes in connection with a primary event of deep venous thrombosis, partly due to a lack of disease-specific measures. The aim here was to develop a disease-specific health-related quality of life (HRQL) measure, the deep venous thrombosis quality of life questionnaire (DVTQOL), for patients with recent exposition and treatment of proximal deep venous thrombosis. METHODS: A total of 121 consecutive outpatients (50 % males; mean age 61.2 +/- 14 years) treated with warfarin (Waran) for symptomatic proximal deep venous thrombosis were included in the study. Patients completed the SF-36, EQ-5D and the pilot version of the DVTQOL. RESULTS: Items having: high ceiling and floor effect, items with lower factor loadings than 0.50 and items loading in several factors were removed from the pilot version of DVTQOL. In addition, overlapping and redundant items identified by the Rasch analysis were excluded. The final DVTQOL questionnaire consists of 29 items composing six dimensions depicting problems with: emotional distress; symptoms (e.g. pain, swollen ankles, cramp, bruising); limitation in physical activity; hassle with coagulation monitoring; sleep disturbance; and dietary problems. The internal consistency reliability was high (alpha value ranged from 0.79 to 0.93). The relevant domains of the SF-36 and EQ-5D significantly correlated with DVTQOL, thereby confirming its construct validity. CONCLUSIONS: The DVTQOL is a short and user-friendly instrument with good reliability and validity. Its test-retest reliability and responsiveness to change in clinical trials, however, must be explored.

Adult↗

[Colored Doppler ultrasound-guided fine-needle aspiration biopsy of portal vein thrombosis: value in diagnosis and assessment of therapeutic efficacy for portal vein thrombosis].

OBJECTIVE: To investigate the value of colored Doppler ultrasound-guided fine-needle aspiration(FNA) biopsy of portal vien thrombosis(PVT) in diagnosis and assessment of therapeutic efficacy for PVT. METHODS: Cytologic findings from 25 portal vien thrombosis patients who underwent FNA were reviewed before and after hepatic arterial chemo-embolization(HAE) and portal vien chemotherapy. RESULTS: 1. Biopsy specimens sufficient for histologic analysis were obtained in all cases (100%). No complications resulted from this procedure. 2. The blood flow within the portal vien with thrombosis could be detected by colored Doppler systems in 25 cases before the patients accepted the treatment. The proliferation and a trabecular cellular arrangement presented in all the cell blocks. Of the 25 cases, 4 (16.0%) demonstrated necrosis of the tumor thrombi and the disappearance of blood flow within portal vein thrombi three weeks after the treatment. Among the 4, 2 were followed-up clinically and underwent second stage resection. 21 (84.0%) cases had no significant change in portal vein thrombosis pathologically and ultrasonically after the treatment. CONCLUSION: Colored Doppler ultrasound-guided FNA biopsy of portal vein thrombi is a safe, accurate, sampling-reliable biopsy technique.

Adult↗

[Biventricular thrombosis in dilated cardiomyopathy. Echocardiographic and pathophysiologic study of intra-cardiac thrombosis].

The paper reports on the observations of biventricular intracardiac thrombosis in dilated cardiomyopathy. The diagnosis was made with the aid of two-dimensional echocardiography used as the method of choice in suspected intracardiac thrombosis. In the authors' opinion, the principal hemostatic disorder in intracardiac thrombosis in dilated cardiomyopathy can be caused by insufficient fibrinolysis whose degree of reduction was confirmed with stimulations tests, some of which were developed at the authors' department. Adequate treatment of intracardiac thrombosis in dilated cardiomyopathy is open to discussion. At present, apart from the standard therapy, the authors mainly suggest anti-coagulation treatment as this can prevent embolization affecting the greater or lesser blood circulation.

Blood Coagulation Disorders↗

Carrageenin-induced thrombosis in the rat and mouse as a test model of substances influencing thrombosis.

Kappa-carrageenins cause disseminated intravascular coagulation with thrombosis of the tail in rats and mice. Frequency and extent of tail thrombosis were used for determining antithrombotic effects after systemic and local external administration of substances. Inhibitors of cyclooxygenase and thromboxane synthetase caused irregular inhibition of thrombosis after relatively high doses. The cyclooxygenase/lipoxygenase inhibitor BW755C was ineffective after 50 mg/kg. Hitherto, no effective substances could be found after external administration on the tail of mice. At present, no convincing explanation for thrombogenic activity of kappa-carrageenin can be given. The advantages of the thrombosis model are discussed.

Animals↗

[Fibrinolysis of deep venous thrombosis on implantable perfusion devices. Apropos of a consecutive series of 57 cases of thrombosis and 32 cases of fibrinolysis].

The main complication of totally implantable venous access devices is deep venous thrombosis on catheter. It may dramatically reduce the already limited venous capacity of patients undergoing chemotherapy and obturate catheters, causing pulmonary embolism or functional disorders. These thromboses usually involve veins of the superior vena cava system where the catheters are implanted. Generally, they occur early, are extensive and often asymptomatic. Doppler ultrasonography is the diagnostic investigation of choice, phlebography being reserved for particular cases or to specify the limits of the thrombus. In a series of 412 vein access devices implanted and systematically monitored by Doppler ultrasonography, we found 57 thromboses (13.8%), 15 partial and 42 complete. The lowest thrombosis rate was observed in the right internal jugular vein (10% vs 20 to 23%, p = 0.006). Thirty-two patients received a systemic fibrinolytic treatment, 16 with streptokinase (SK), five with urokinase (UK), four with tissue plasminogen activator (rt-PA) and seven with SK/UK association. No serious side effects were observed. Sixteen repermeabilizations (50% of fibrinolysis) were obtained. There were no significant differences with respect to the fibrinolytic, the initial characteristics of thrombosis or the patients. Patients without fibrinolysis received 3 weeks of low molecular weight heparin (curative doses) then warfarin. Only one patient was repermeabilized with this treatment (significative difference with fibrinolysis: p = 0.009). Fibrinolysis is indicated in symptomatic thrombosis and/or in cases of extension to the innominate vein or the superior vena cava. Systematic monitoring by Doppler ultrasonography and prophylactic anti-thrombotic treatment are recommended in patients with implantable venous access devices in order to decrease the occurrence of thromboses, to detect asymptomatic patients at an early stage and to increase the effectiveness of fibrinolysis.

Adult↗

Sinus thrombosis after a jump from a small rock and a sneezing attack: minor endothelial trauma as a precipitating factor for cerebral venous thrombosis?

Cerebral venous thrombosis (CVT) associated with minor or trivial head trauma has only been described in a few cases so far. We report two patients who developed CVT after a sudden intracranial pressure increase and head acceleration. A 49-year-old woman jumped from a small rock, 1 m in height, and developed instantaneous occipital headaches. Magnetic resonance imaging (MRI) confirmed confluens sinuum thrombosis. Risk factors consisted of smoking and oral contraceptives. Our second patient, an 18-year-old woman, experienced instantaneous headaches after a sneezing attack. Superior sagittal and right-sided transverse sinus thrombosis were confirmed by venous computed tomography angiography. She took oral contraceptives as an additional risk factor. In about 20% of CVT cases the cause remains unclear. As minor head trauma may not have been recognized during history taking, this may represent a so far under-recognized precipitating factor for CVT.

Adolescent↗

Prevalence and distribution of calf vein thrombosis in patients with symptomatic deep venous thrombosis: a color-flow duplex study.

PURPOSE: This retrospective study was performed to identify the patterns of calf vein thrombosis in patients in whom deep vein thrombosis (DVT) was suspected and to better define the role of color-flow duplex scanning (CDS) in the evaluation of this patient population. METHODS: Over a recent 9-month period, we reviewed the vascular laboratory charts of 540 symptomatic patients (696 limbs) who underwent CDS for clinically suspected acute DVT. Patients who had a previous episode of DVT were excluded. RESULTS: CDS satisfactorily visualized all three paired calf veins in 655 of the limbs (94%). Inadequate scans (n = 41) were attributed to edema in 29, excessive calf size in eight, and anatomic inaccessibility in four. Peroneal veins were the most difficult to visualize (n = 29), followed by posterior tibial (n = 10) and anterior tibial (n = 9) veins. CDS identified acute DVT in 159 of 655 limbs (24%) that had adequate scans. Calf vein thrombi were detected in 110 of the 655 limbs (17%) and in 69% of the 159 limbs with DVT. Clots were confined to the calf veins in 53 limbs with DVT (33%). Isolated calf vein thrombi were found in 45% of outpatient limbs and in 27% of inpatient limbs with DVT. The peroneal (81%) and posterior tibial veins (69%) were more frequently involved (p < 0.001) than the anterior tibial veins (21%). In limbs with calf DVT, the prevalence of thrombosis isolated to the peroneal and posterior tibial veins was similar (37% and 25%, respectively); no limb had an isolated anterior tibial DVT (p = 0.02). CONCLUSION: CDS is a reliable method for evaluating calf veins for DVT. Calf vein thrombosis is common in patients who have acute DVT and often occurs as an isolated finding. The peroneal and posterior tibial veins are involved in the majority of cases; thrombi occur much less frequently in the anterior tibial veins. We conclude that CDS should be the noninvasive method of choice for the initial evaluation of patients in whom DVT is suspected, and we recommend that calf veins should always be studied but that routine scanning of the anterior tibial veins may not be necessary.

Acute Disease↗

[20210G/A mutation of prothrombin gene in a patient with deep venous thrombosis ad pulmonary embolism without other risk factors of thrombosis].

A new genetic anomaly predisposing to venous thrombosis was described in 1996, namely the transition of guanine (G) to adenine (A) at position 20210 in the 3-untranslated region of the prothrombin gene. This mutation is associated with high levels of plasma prothrombin and increased risk of thrombotic events in the venous system. We report the case of a man who, lacking known risk factors for thrombosis, suffered a massive pulmonary embolism and deep venous thrombosis in both lower legs. Thrombophilic analysis confirmed that the patient and close relatives were carriers of the heterozygotic 20210G/A variant of the prothrombin gene. Two relatives with the genetic defect had also suffered some type of deep venous thrombosis.

Adult↗

[Sequelae of venous thrombosis. Incidence in of the post-thrombosis syndrome after 5 years].

The authors report on an epidemiological study carried out in Basle, Switzerland, which prospectively included 341 consecutive patients (226 men, 115 women, mean age 52 +/- 16 years) who had developed deep venous thrombosis evidenced by phlebography. The treatment of the acute phase most often consisted in thrombolysis, conventional heparin being reserved for the contra-indications of thrombolysis. A second phlebographic examination allowed dividing up the series into two groups, ie. positive and negative, according to the presence or absence of a complete or partial return of patency. Each group was subdivided according to the location and extension of the thrombosis. Both groups (positive vs. negative) are different as regards the location and extent of the thrombosis. The selective comparison of both groups according to the objective subdivision demonstrated: the absence of post-phlebitis disease in sural phlebitis; the same risk of post-phlebitis disease in thrombosis extending to 4 levels, whether patency was restored or not; lower incidence of post-phlebitis disease in the positive group for single -, two - or three-level phlebitis. Leg ulcers occur within an average of 5.5 +/- 2.1 years after the acute episode in 6.7% of all patients. Complete return of patency is obtained in 23% of cases only.

Adult↗

Massive acute thrombosis of the descending thoracic aorta in heparin-associated thrombocytopenia and thrombosis.

Heparin-associated thrombocytopenia with thrombosis is a rare but serious complication in patients receiving heparin therapy. We report a case of a patient with this complication who had massive thrombosis within the descending thoracic aorta detected by transesophageal echocardiography. Our case suggests that a transesophageal echocardiographic examination can be useful in the early diagnosis of heparin-associated thrombocytopenia and thrombosis.

Acute Disease↗

Evaluation of thrombolysis and angioplasty in a porcine iliac artery thrombosis model: application of endovascular stent-graft-induced thrombosis.

PURPOSE: To develop a novel endovascular thrombosis model in the porcine iliac artery for the evaluation of thrombolysis and angioplasty. MATERIALS AND METHODS: A stent-inversion-graft (SIG) model combining either a 3-mm or 5-mm tapered expandable polytetrafluoroethylene (ePTFE) graft attached within a self-expandable, 10-mm nitinol stent was placed in the left common iliac artery via an ipsilateral common femoral artery approach in 24 pigs. When the iliac artery was thrombosed, urokinase (250,000 IU) plus heparin (1,000 units) were pulse sprayed via a contralateral femoral approach (n = 12). Saline pulse-spray was used as a control group (n = 12). Balloon angioplasty was performed to eliminate the stenotic tapered graft within the stent after successful thrombolysis. The efficacy of the thrombolysis was assessed with use of intravascular ultrasound (IVUS) and arteriogram. RESULTS: Both the 3-mm tapered and 5-mm tapered SIG models caused iliac artery occlusion in 22 +/- 5 and 41 +/- 9 minutes, respectively, after the deployment. Luminal patency was re-established successfully in all occluded arteries after urokinase infusion. Angioplasty was successful in eliminating the tapered stenosis and restoring the normal diameter in all iliac arteries treated with urokinase. Complete thrombolysis was achieved in both models treated with urokinase. CONCLUSION: This novel endovascular approach of inducing arterial thrombosis is simple to perform and reliably produces arterial thrombosis. The intraluminal stenosis is also amenable to angioplasty. This model is useful for the evaluation of antithrombotic treatment modality and adjunctive endovascular interventions.

Alloys↗

Thrombosis and thrombolysis in crushed arteries with or without anastomosis: a new microvascular thrombosis model.

This study introduces a new rat thrombosis model in which a 2-mm segment of femoral artery is crushed by an impact load. Ninety-five femoral arteries were divided into five groups. The vessels in Groups I and 2 underwent only crush injuries with a 15-kg and 25-kg load, respectively. Group 3 vessels were not crushed, but did undergo vessel anastomosis by a standard microsurgical technique. The vessels in Groups 4 and 5 were crushed by a 25-kg load, and then divided and anastomosed. During the procedure, the vessel lumina were topically irrigated with saline (Group 4) or heparin solution (Group 5). Thrombosis and thrombolysis were evaluated at set time points up to 56 days after operation. While all vessels in Groups 1 and 3 remained patent, the rate of occlusive thrombus formation in Group 2 significantly (p < 0.001) dropped from 85 percent at day 1 to 11 percent at day 7. The intima and media in Groups 4 and 5 were severely disrupted and often occluded the lumen, Group 5 had a significantly (p < 0.01 to 0.001) lower rate of occlusive thrombus formation (40 to 45 percent) at days 1 and 7 than Group 4 (90 percent). Histology in Groups 2, 4, and 5 at day 1 showed no intimnal and almost no medial tissue left in the crushed area. The adventitia and remaining external elastic lamina were adherent to thrombus in the occluded vessels or covered by fibrin and platelet mesh in the patent vessels. The results documented that spontaneous thrombolysis occurs in thrombosed arteries following crush injury alone, but not in thrombosed arteries after crush injury followed by suture anastomoses. The degree of disruption of the internal elastic lamina and the presence of sutures appear to contribute to occlusive thrombus formation following crush injury and anastomoses. Topical irrigation with heparin solution, at the concentration routinely used clinically, significantly reduces the thrombosis rate at the anastomosis site in crushed vessels, but does not promote thrombolysis.

Anastomosis, Surgical↗

Treatment of experimentally induced caval thrombosis with oral low molecular weight heparin and delivery agent in a porcine model of deep venous thrombosis.

OBJECTIVE: This experiment evaluated enterally administered low molecular weight heparin (LMWH) combined with sodium N-[10-(2-hydroxybenzoyl)amino] decanoate (SNAD) for the treatment of induced venous thrombosis. SUMMARY BACKGROUND DATA: SNAD is a delivery agent that potentiates the gastrointestinal absorption of LMWH. METHODS: Forty female pigs were equally assigned to four groups: control (saline); enteral LMWH, 2,000 IU/kg; enteral SNAD, 50 mg/kg; and enteral LMWH, 2,000 IU/kg and SNAD, 50 mg/kg. Under fluoroscopic guidance, the infrarenal vena cava was occluded with a balloon catheter. Two milliliters of ethanol was injected into the distal vena cava. The inflated balloon catheter remained in situ for 5 days, at which time animals angiographically exhibiting thrombus were randomly assigned to the four groups. Study medications were dosed at 12-hour intervals by means of a gastrostomy tube placed previously. After 7 days of treatment, thrombus was extracted. A separate group of 10 animals was used to measure plasma antifactor Xa levels for 6 hours after enteral dosing of LMWH/SNAD. RESULTS: The amount of residual thrombus after treatment with enteral LMWH/SNAD was significantly decreased. Antifactor Xa levels were significantly elevated in the LMWH/SNAD group versus baseline. CONCLUSION: The combination of enterally administered LMWH and SNAD given for 7 days appeared to decrease caval thrombosis in this model of deep vein thrombosis. Enteral LMWH/SNAD effected an increase in plasma levels of antifactor Xa.

Animals↗

Oral L-arginine administration does not inhibit thrombosis on an experimental model of arterial thrombosis: the effect on the apyrasic activity of the arterial wall.

Despite the extensive research on the pharmacology of L-arginine, there are only few data on its antithrombotic properties. We studied the effect of oral L-arginine administration in a model of arterial thrombosis in rabbits divided into three groups: group 1, group without intervention; group 2, control group, treated with normal diet and submitted to the thrombosis-triggering protocol; group 3, treated for 2 weeks with L-arginine (2.25%) prior the protocol. L-Arginine did not alter platelet aggregation nor coagulation parameters but reduced vascular activities of both ADPase (49.1 +/- 8.5 versus 28.9 +/- 8.3 versus 18.8 +/- 10.3 nmoles inorganic phosphate/min per mg protein; mean +/- SD; group 1 versus group 2 versus group 3, respectively; ANOVA F = 19.21; P < 0.0001) and ATPase (97.8 +/- 15.8 versus 52.1 +/- 11.6 versus 31.9 +/- 16.3 nmoles inorganic phosphate/min per mg protein; mean +/- SD; group 1 versus group 2 versus group 3, respectively; ANOVA, F = 34.65; P < 0.0001). L-Arginine did not reduce the thrombi area (17.1 mm, 9.02 and 48.07, versus 27.04 mm, 25.4 and 70.39, median, percentile 25 and 75 respectively, P = 0.079; group 2 versus group 3, respectively). In conclusion, oral L-arginine administration did not inhibit thrombosis, and, conversely, it significantly reduced the arterial wall ADPase and ATPase activities. This effect may limit its antithrombotic properties.

Adenosine Triphosphatases↗

Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT).

BACKGROUND AND PURPOSE: The natural history and long-term prognosis of cerebral vein and dural sinus thrombosis (CVT) have not been examined previously by adequately powered prospective studies. METHODS: We performed a multinational (21 countries), multicenter (89 centers), prospective observational study. Patients were followed up at 6 months and yearly thereafter. Primary outcome was death or dependence as assessed by modified Rankin Scale (mRS) score >2 at the end of follow-up. RESULTS: From May 1998 to May 2001, 624 adult patients with CVT were registered. At the end of follow-up (median 16 months), 356 patients (57.1%) had no symptom or signs (mRS=0), 137 (22%) had minor residual symptoms (mRS=1), and 47 (7.5%) had mild impairments (mRS=2). Eighteen (2.9%) were moderately impaired (mRS=3), 14 (2.2%) were severely handicapped (mRS=4 or 5), and 52 (8.3%) had died. Multivariate predictors of death or dependence were age >37 years (hazard ratio [HR]=2.0), male sex (HR=1.6), coma (HR=2.7), mental status disorder (HR=2.0), hemorrhage on admission CT scan (HR=1.9), thrombosis of the deep cerebral venous system (HR=2.9), central nervous system infection (HR=3.3), and cancer (HR=2.9). Fourteen patients (2.2%) had a recurrent sinus thrombosis, 27 (4.3%) had other thrombotic events, and 66 (10.6%) had seizures. CONCLUSIONS: The prognosis of CVT is better than reported previously. A subgroup (13%) of clinically identifiable CVT patients is at increased risk of bad outcome. These high-risk patients may benefit from more aggressive therapeutic interventions, to be studied in randomized clinical trials.

Adolescent↗

Laser-induced thrombosis in zebrafish larvae: a novel genetic screening method for thrombosis.

Classical genetic approaches to study hemostasis and thrombosis have not been available until our recent introduction of the teleost, Danio rerio (the zebrafish), as an effective genetic model for in vivo coagulation assays. The genetic screen for this model is carried out using the genome saturation mutagenesis approach. The resulting mutants are screened for hemostatic or thrombotic defects. We developed a global physiological screening method for thrombosis by utilizing a laser to induce thrombosis in a specifically targeted area of the major artery and vein. Using this assay, we have screened many fish for abnormal hemostasis, and have isolated a number of mutants with abnormal coagulation parameters. These mutants can be grown, bred, and further evaluated for the genetic etiology of their abnormal hemostatic pathways.

Animals↗